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Drug Interactions between fosphenytoin and K2-D3

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

cholecalciferol fosphenytoin

Applies to: K2-D3 (cholecalciferol / menaquinone) and fosphenytoin

MONITOR: Coadministration with potent CYP450 3A4 inducers and certain anticonvulsants, which are also capable of CYP450 3A4 induction, may decrease the pharmacologic effects of vitamin D and/or vitamin D analogs. In general, vitamin D is primarily biotransformed into inactive metabolites via CYP450 3A4 in the liver. Increases in the inactivation of vitamin D may be accompanied by reduced serum calcium and increased parathyroid hormone levels. Patients on long-term anticonvulsant therapy have occasionally developed osteomalacia, presumably due to interference with vitamin D and calcium metabolism. Clinical studies have documented widely varying rates of vitamin D deficiency in pediatric patients being treated with anticonvulsants, ranging from as low as 10% to as high as 79%. Case reports of low vitamin D levels associated with symptomatic hypocalcemia also exist in patients on the potent CYP450 3A4 inducer, rifampin.

MANAGEMENT: Patients receiving vitamin D and/or vitamin D analogs with potent CYP450 3A4 inducers or anticonvulsants capable of CYP450 3A4 induction should be monitored more closely for reduced vitamin D effects. Higher doses of vitamin D and/or the vitamin D analog may be necessary to achieve the desired therapeutic effect.

References (16)
  1. (2023) "Product Information. Drisdol (ergocalciferol)." Validus Pharmaceuticals LLC
  2. (2023) "Product Information. Alfacalcidol (alfacalcidol)." Strides Pharma UK Ltd
  3. (2024) "Product Information. Fultium-D3 (colecalciferol)." Internis Pharmaceuticals Ltd
  4. (2024) "Product Information. Ostelin Specialist Range Vitamin D (colecalciferol)." Sanofi-Aventis Healthcare Pty Ltd T/A Sanofi Consumer Healthcare
  5. (2021) "Product Information. Rocaltrol (calcitriol)." Atnahs Pharma UK Ltd
  6. (2019) "Product Information. Calcitriol (calcitriol)." Strides Pharma Inc.
  7. (2024) "Product Information. Calcitriol (GenRx) (calcitriol)." Apotex Pty Ltd
  8. (2022) "Product Information. Ergocalciferol (ergocalciferol)." RPH Pharmaceuticals AB
  9. (2020) "Product Information. Sandoz D (cholecalciferol)." Sandoz Canada Incorporated
  10. (2022) "Product Information. Zemplar (paricalcitol)." AbbVie Ltd
  11. (2012) "Product Information. Zemplar (paricalcitol)." Abbott Laboratories, Limited
  12. (2023) "Product Information. Doxercalciferol (doxercalciferol)." Chartwell RX, LLC.
  13. (2024) "Product Information. Rayaldee (calcifediol)." OPKO Pharmaceuticals LLC
  14. Kasarla SS, Garikapati V, Kumar Y, Dodoala S (2024) Interplay of vitamin D and CYP3A4 polymorphisms in endocrine disorders and cancer. https://e-enm.org/journal/view.php?doi=10.3803/EnM.2021.1349
  15. Saket S, Varasteh N, Halimi Asl AA, Saneifard H (2024) How antiepileptics may change the serum level of vitamin D, calcium, and phosphorus in children with epilepsy. https://journals.sbmu.ac.ir/ijcn/article/view/25952
  16. Leung C, warner j, Harris M, Nourse C (2016) "Symptomatic hypocalcemia secondary to rifampicin-induced hypovitaminosis D." Pediatr Infect Dis J, 35, p. 822-3

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Drug and food interactions

Moderate

cholecalciferol food

Applies to: K2-D3 (cholecalciferol / menaquinone)

MONITOR: Additive effects and possible toxicity (e.g., hypercalcemia, hypercalciuria, and/or hyperphosphatemia) may occur when patients using vitamin D and/or vitamin D analogs ingest a diet high in vitamin D, calcium, and/or phosphorus. The biologically active forms of vitamin D stimulate intestinal absorption of calcium and phosphorus. This may be helpful in patients with hypocalcemia and/or hypophosphatemia. However, sudden increases in calcium or phosphorus consumption due to dietary changes could precipitate hypercalcemia and/or hyperphosphatemia. Patients with certain disease states, such as impaired renal function, may be more susceptible to toxic side effects like ectopic calcification. On the other hand, if dietary calcium is inadequate for the body's needs, the active form of vitamin D will stimulate osteoclasts to pull calcium from the bones. This may be detrimental in a patient with reduced bone density.

MANAGEMENT: Given the narrow therapeutic index of vitamin D and vitamin D analogs, the amounts of calcium, phosphorus, and vitamin D present in the patient's diet may need to be taken into consideration. Specific dietary guidance should be discussed with the patient and regular lab work should be monitored as indicated. Calcium, phosphorus, and vitamin D levels should be kept within the desired ranges, which may differ depending on the patient's condition. Patients should also be counseled on the signs and symptoms of hypervitaminosis D, hypercalcemia, and/or hyperphosphatemia.

References (10)
  1. (2023) "Product Information. Drisdol (ergocalciferol)." Validus Pharmaceuticals LLC
  2. (2024) "Product Information. Fultium-D3 (colecalciferol)." Internis Pharmaceuticals Ltd
  3. (2024) "Product Information. Ostelin Specialist Range Vitamin D (colecalciferol)." Sanofi-Aventis Healthcare Pty Ltd T/A Sanofi Consumer Healthcare
  4. (2021) "Product Information. Rocaltrol (calcitriol)." Atnahs Pharma UK Ltd
  5. (2019) "Product Information. Calcitriol (calcitriol)." Strides Pharma Inc.
  6. (2024) "Product Information. Calcitriol (GenRx) (calcitriol)." Apotex Pty Ltd
  7. (2022) "Product Information. Ergocalciferol (ergocalciferol)." RPH Pharmaceuticals AB
  8. (2020) "Product Information. Sandoz D (cholecalciferol)." Sandoz Canada Incorporated
  9. Fischer V, Haffner-Luntzer M, Prystaz K, et al. (2024) Calcium and vitamin-D deficiency marginally impairs fracture healing but aggravates posttraumatic bone loss in osteoporotic mice. https://www.nature.com/articles/s41598-017-07511-2
  10. National Institutes of Health Office of Dietary Supplements (2024) Vitamin D https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/#h37

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

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